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Forced Unfolding of Apocytochrome b 5 by Steered Molecular Dynamics Simulation

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Abstract

Apocytochrome b 5 (apocyt b 5), a small b-type cytochrome with heme prosthetic group removal, has been subjected to steered molecular dynamics (SMD) simulations for investigating the consequences of mechanical force-induced unfolding. Both constant velocity (0.5 and 1.0 Å/ps) and constant force (500, 750 and 1000 pN) stretching have been employed to model forced unfolding of apocyt b 5. The results of SMD simulations elucidate that apocyt b 5 is protected against external stress mainly through the interstrand hydrogen bonding between its β1–β2 and β2–β3 strands, highlighting the importance of hydrophobic core 2 in stabilization of apocyt b 5. The existence of intermediate states manifested by current simulations in the forced unfolding pathway of apocyt b 5 is different from the observations in pervious thermal or chemical unfolding studies in the absence of force. The present study could thus provide insights into the relationship between the two cooperative functional modules of apocyt b 5 and also guide the rational molecular design of heme proteins.

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Abbreviations

cyt b 5 :

Cytochrome b 5

apocyt b 5 :

Apocytochrome b 5

holocyt b 5 :

Holocytochrome b 5

cyt c :

Cytochrome c

AFM:

Atomic force microscopy

NMR:

Nuclear magnetic resonance

SMD:

Steered molecular dynamics

cv-SMD:

Constant velocity SMD

cf-SMD:

Constant force SMD

RMSD:

Root mean square deviation

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Authors and Affiliations

  1. College of Chemistry and Chemical Engineering, University of South China, Hunan, Hengyang, 421001, P.R. China

    Ying-Wu Lin

  2. Chemical Biology Lab, Department of Chemistry, Fudan University, Shanghai, 200433, P.R. China

    Ying-Wu Lin, Zhong-Hua Wang, Feng-Yun Ni & Zhong-Xian Huang

Authors
  1. Ying-Wu Lin
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  2. Zhong-Hua Wang
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  3. Feng-Yun Ni
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  4. Zhong-Xian Huang
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Correspondence to Ying-Wu Lin.

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Lin, YW., Wang, ZH., Ni, FY. et al. Forced Unfolding of Apocytochrome b 5 by Steered Molecular Dynamics Simulation. Protein J 27, 197–203 (2008). https://doi.org/10.1007/s10930-007-9125-9

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  • DOI: https://doi.org/10.1007/s10930-007-9125-9

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